Review Article

Noninvasive Brain Stimulations for Unilateral Spatial Neglect after Stroke: A Systematic Review and Meta-Analysis of Randomized and Nonrandomized Controlled Trials

Table 2

Study characteristics related to design of study, setting, number of participants, mean age, gender, and inclusion and exclusion criteria.

Author, yearDesign of studyStatus of publicationLocationNo. of participantsMean ageNo. of males (%)Inclusion criteriaExclusion criteria

Randomized controlled trials
Cao et al., 2016 [50]Parallel RCTFull textAsiaI: 7
C: 6
I: 55.0
C: 62.0
I: 85.7
C: 83.3
Right-handed patients who had a first-ever stroke in the right hemisphere and visuospatial neglect with normal or corrected-to-normal visionNR
Cha and Kim, 2016 [51]Parallel RCTFull textAsiaI: 15
C: 15
I: 64.07
C: 63.33
I: 64
C: 60.0
Had a first right hemisphere stroke (cerebral infarction or hemorrhage) more than 2 weeks before the study, which had been confirmed by computed tomography or magnetic resonance imaging (MRI); had VSN determined by line bisection tests (rightward bias > 12%) or star cancelation test (omission of any number of stars); had a Glasgow coma scale score < 15; 18–80 years old; right-handed; normal vision or normal corrected vision; and had the ability to understand the study and signed an informed consent formAll patients did not have brain tumors or other brain pathology.
Excluded were patients with hemianopia; subarachnoid hemorrhage, venous sinus thrombosis, transient ischemic attack, reversible ischemia, or a condition exacerbated by a new infarction or hemorrhage site; a medical history or family history of seizure; or with metal devices or claustrophobia preventing MRI
Fu et al., 2015 [52]Parallel RCTFull textAsiaI: 11
C: 11
I: 55.1β
C: 59.5β
I: 80.0
C: 80.0
Right-handed patients with right hemisphere stroke (hemorrhagic or ischemic lesion) confirmed by computed tomography or magnetic resonance imaging > 2 weeks before the beginning of the study and diagnosis of visuospatial neglect based on clinician judgement and on deficits in at least one out of two paper-pencil testsAge < 30 years or > 80 years, history of epilepsy, previous head trauma, drug and alcohol abuse and psychiatric disorders, recurrent stroke, obvious aphasia and communication obstacles, family history of seizures, ever use of tricyclic antidepressants or antipsychotic drugs, diamagnetic metal implants such as cardiac pacemakers, and visual field defects
Fu et al., 2017 [60]Parallel RCTFull textAsiaI: 6
C: 6
I: 60.17
C: 62
I: 75
C: 75
Had a first right hemisphere stroke (cerebral infarction or hemorrhage) more than 2 weeks before the study, which had been confirmed by computed tomography or magnetic resonance imaging (MRI); had VSN determined by line bisection tests (rightward bias > 12%) or star cancelation test (omission of any number of stars); had a Glasgow coma scale score < 15; 18–80 years old; right-handed; normal vision or normal corrected vision; and had the ability to understand the study and sign an informed consent form; all patients did not have brain tumors or other brain pathologyPatients with hemianopia; subarachnoid hemorrhage, venous sinus thrombosis, transient ischemic attack, reversible ischemia, or a condition exacerbated by a new infarction or hemorrhage site; a medical history or family history of seizure; or with metal devices or claustrophobia preventing MRI
Smit et al., 2015 [56]RCT cross-over studyFull textEuropeI: 5
C: 5
I: 64.8
C: 64.8
I: 60.0
C: 60.0
Patients with left hemispatial neglect after right-hemispheric lesion, right-handed, older than the age of 18, more than four months after strokePatients with severe language and communication disorders, bilateral cortical damage, psychiatric disorders, alcohol and/or drug addiction, epilepsy, eczema or damages on the scalp, metal or other foreign parts in the head
Yang et al., 2015 [55]Parallel RCTFull textAsiaI: 9
I2: 10
I3: 9
C: 10
I: 46.7
I2: 48.0
I3: 49.4
C: 47.7
I: 66.6
I2: 40.0
I3: 55.6
C: 30.0
Age between 18 and 80; first stroke patients (cerebral infarction or hemorrhage) and in recovery time within 60–180 days; USN confirmed by line bisection test, star cancellation test, or clinical examination; no metallic implant of diamagnetic substance; signed the informed consentSubarachnoid hemorrhage, venous sinus thrombosis, and reversible or transient ischemic attacks; worsening condition and new-onset infarction or hemorrhage; GCS score < 15; obvious aphasia and severe cognitive-communicationdisorders; family history of epilepsy; impaired organ function or failure in the heart, lung, liver, kidney, or other vital organs and life expectancy < 6 months; history of claustrophobia and uncooperative during examination; and hemianopsia
Kim et al. [53]Parallel RCTFull textAsiaI: 9
I2: 9
C: 9
I: 68.6
I2: 64.1
C: 68.3
I: 55.6
I2: 44.4
C: 66.7
Patients with right cerebral ischemic or hemorrhagic with visuospatial neglect (confirmed using the line bisection test); all patients were right-handedSevere cognitive impairment making them unable to understand the instructions; contraindications for TMS, such as a history of epileptic seizure, major head trauma, and presence of metal in the skull or pacemaker; or unstable medical or neurologic conditions
Sunwoo et al., 2013 [57]RCT cross-over studyFull textAsiaI: 10
I2: 10
C: 10
62.6¢40.0βStroke patients with lesion in the right hemisphere involving the parietal cortex, and left USN diagnosed by clinical observation and confirmed by a line bisection test; all patients were previously right-handedPatients who had metallic implants in the cranial cavity, a skull defect, history of seizure, uncontrolled medical problems, and severe cognitive impairment
Cazzoli et al., 2012 [14]Parallel RCTFull textEurope24£58.0¢70.8¢Ischemic or hemorrhagic lesion to the right hemisphere and left-sided spatial neglect determined on the basis of deficits in at least two out of three classes of paper-pencil tests and on clinical judgement; all patients had to have normal or corrected-to-normal visual acuityHistory of epilepsy, prior head trauma, drug and alcohol abuse, and major psychiatric disorders
Ko et al., 2008 [58]RCT cross-over studyFull textAsiaI: 15
C: 15
I: 62.1
C: 62.1
I: 66.6
C: 66.6
Patients with subacute stroke with neglectPatients who had metal in the cranial cavity or calvarium, skin lesions in the area of electrode, uncontrolled medical conditions, and severe cognitive impairments
Koch et al., 2012 [54]Parallel RCTFull textEuropeI: 10
C: 10
I: 61.4#
C: 71.9#
I: 55.5#
C: 55.5#
Right-handed patients, with right hemisphere subacute ischemic stroke affected by hemispatial neglect, confirmed by radiologic (CT or MRI) and clinical examinationNR
Bonnì et al., 2011 [59]Parallel RCTConference abstractEuropeNRNRNRSubacute stroke patients with neglectNR
Non-RCTs
Cazzoli et al., 2015 [61]Non-RCT cross-over study§Full textEuropeI: 8¥
C: 8¥
I: 52.6 and 54.2α
C: 53.0
NRPatients with left-sided, hemispatial neglect after a subacute right-hemispheric stroke; all patients had normal or corrected-to-normal visual acuityNot clearly reported, however, authors have assessed patients by means of internationally accepted safety guidelines for the application of TMS, which included screening for a history of epilepsy, prior head trauma, drug and alcohol abuse, and major psychiatric disorders
Hopfner et al., 2015 [62]Non-RCT cross-overFull textEuropeI: 18
C: 18
I: 64.5
C: 64.5
I: 50.0
C: 50.0
Left-sided neglect, based on clinical judgement and neuropsychological testing, after subacute right-hemispheric stroke; all subjects had normal or corrected-to-normal visual acuityNR
Làdavas et al., 2015 [64]Quasi-RCTFull textEuropeI: 8
I2: 11
C: 11
I: 72.0
I2: 66.0
C: 67.0
I: 50.0
I2: 54.5
C: 54.5
Patients with right hemisphere stroke with hemispatial neglect and performance on the Behavioral Inattention Test battery with scores ≤ 129Presence of widespread mental deterioration (Mini-Mental State Examination score < 20), psychiatric disorders, a history of prior stroke or hemorrhage, any severe internal medical disease, epilepsy, and additional factors influencing the risk of epilepsy
Agosta et al., 2014 [63]Non-RCT cross-over studyFull textEuropeI: 6
C: 6
I: 67.83
C: 67.83
I: 66.6
C: 66.6
Patients with right hemisphere unilateral lesions due to a cerebrovascular stroke, confirmed by radiological examination (CT or MR), in their chronic stage after the stroke (at least six months post onset); besides, participants were right-handed, native Italian speakers, and had normal or corrected-to-normal visual acuityHistory or evidence of degenerative disease or psychiatric disorder

C: control group; CT: computed tomography; GCS: Glasgow coma scale; I: intervention; MR: magnetic resonance imaging; No.: number; RCT: randomized controlled trial; TMS: transcranial magnetic stimulation; USN: unilateral spatial neglect. Participants of the experimental group also served as controls. ¥Five patients were randomized in parallel design, and three further patients included in both groups. £The authors did not specify the sample size per studied group. αData comprises three patients that received both experimental and control interventions. βData was calculated from 10 patients (one patient was excluded after randomization). ¢Data are from the whole sample, as the authors did not specify it per studied group. #Data are from 9 patients in each group. §The study was a cross-over for only three patients, for the remaining ten patients the study was a RCT.